crossing96/oncoscreening huggingface dataset:
Measurement of plasma concentration of gemcitabine and its metabolite dFdU in hemodialysis patients with advanced urothelial cancer.	OBJECTIVE: We investigated the pharmacokinetics of gemcitabine and its metabolite in two male patients (52 and 56-year-old) with advanced urothelial cancer receiving hemodialysis three times a week. METHODS: Gemcitabine, 1000 mg/m(2) in 100 ml of saline, was intravenously administered for 30 min. The concentration of gemcitabine and its metabolite 2',2'-difluorodeoxyuridine (dFdU) was measured at several given time points using a high-pressure liquid chromatography assay. Pharmacokinetic parameters were determined using the two-compartment modeling program. RESULTS: Gemcitabine was rapidly eliminated from plasma even in patients with renal dysfunction. No obvious differences in pharmacokinetic parameters such as the t(1/2), AUC and C(max) of gemcitabine were observed between the patients on hemodialysis and those with normal renal function in previous reports. On the other hand, dFdU showed a sustained level until hemodialysis was initiated. Hemodialysis could reduce the plasma dFdU level by approximately 50%. CONCLUSIONS: According to the previous information, no dose modification of gemcitabine may be required for patients with renal impairment or hemodialysis. However, gemcitabine should be given with caution because only limited information is available, and the clinical effect of sustained and/or accumulated dFdU is unknown.	bladder
Inflammatory myofibroblastic tumor of the urinary bladder in a 27-year-old woman with systemic lupus erythematosus.	Spindle cell lesions of the urinary bladder are uncommon tumors, and are most often spindle cell (sarcomatoid) carcinomas, non-neoplastic reactive mesenchymal proliferations, or soft tissue sarcomas. Inflammatory myofibroblastic tumors (IMTs) may also occur in this location. Herein, we report an unusual case of an IMT arising in a previously uninstrumented bladder of a 27-year-old African American female with systemic lupus erythematosus. To our knowledge, IMT has not been reported in the clinical setting of rheumatologic disease.	bladder
[Molecular targeting therapy for bladder cancer].	Molecular-targeted drugs are agents that act on molecules which are specifically expressed in cancer, or on molecules whose expression is increased in cancer compared to normal tissue, and suppress the growth, infiltration and metastasis of cancer while affecting normal tissue as little as possible by selectively impairing function in cancer tissue. The major molecular targets in cancer therapy include oncogene products, growth factors and their receptors, signal-transducing molecules, hormone receptors, cell cycle-related proteins, telomerase-related molecules, apoptosis-related molecules, angiogenesis-related molecules, anticancer drug resistance/sensitivity factors, transcription factors, and molecules related to infiltration and metastasis. This paper reports on the molecular-targeted drugs currently considered for bladder cancer.	bladder
A total hip replacement infected with mycobacterium bovis after intravesicular treatment with Bacille-Calmette-Guérin for bladder cancer.	An 86-year-old male presented with a loose total hip replacement (THR) ten years after implantation. At revision for anticipated aseptic loosening, watery pus was found in the joint and Bacille-Calmette-Guérin (BCG) was seen on culture. The bacterial strain was identified and was identical to the BCG used in the intravesicular treatment of superficial bladder carcinoma in this patient ten months earlier. After revision he received a full course of antituberculous treatment. The clinical and radiological results were excellent after follow-up for 30 months with his uncemented THR showing satisfactory incorporation. His inflammatory markers were normal and his Harris hip score was 95 points. The diagnosis of a tuberculous infection can be easily missed, but must be considered, especially if sterile pus is encountered.	bladder
[Endoluminal therapy for bilateral malignant ureteric obstruction].	OBJECTIVE: To evaluate the endourological technique in the treatment of bilateral malignant ureteric obstruction. METHODS: The data of 43 patients (totally, 70 cases) with bilateral malignant ureteric obstruction treated with endoluminal therapy were reviewed retrospectively. Of 70 cases, 38 were treated by retrograde double-J stenting, 24 by minimally invasive percutaneous nephrotomy (MPCN) and 8 by antegrade double-J stenting. RESULTS: All patients were followed up for an average of 12 months. The retrograde double-J stenting, MPCN and antegrade double-J stenting was successfully performed in 50.0% (19/38), 100.0% (24/24) and 62.5% (5/8), respectively. Technical failures in placing retrograde double-J stent were too difficult to identify the ureteric orifice (13/38) or failing to cross the obstruction site because of severe extraluminal compression (6/38). Failure in placing antegrade double-J stent was due to severe extraluminal compression (3/8). Dislodgment of nephrostomy tubes (11/19) was the major factor which limited the application of MPCN. CONCLUSION: It is safe and effective to treat malignant ureteric obstruction with endourological technique, and suggested initially with retrograde double-J stenting. If malignant ureteric orifice occlusion or a severe extraluminal compression is showed in the imaging, MPCN or antegrade double-J stenting may be selected according to the site and the extent of obstruction.	bladder
Protein expression and amplification of AIB1 in human urothelial carcinoma of the bladder and overexpression of AIB1 is a new independent prognostic marker of patient survival.	AIB1, a candidate oncogene in human breast cancer, is frequently amplified and overexpressed in several types of human cancers, but the status of AIB1 amplification and expression in urothelial carcinoma of the bladder (UC) and its clinical/prognostic significance is unclear. In our study, the methods of immunohistochemistry and fluorescence in situ hybridization were utilized to examine protein expression and amplification of AIB1 in 163 primary UCs and in 30 samples of normal bladder mucosa. Overexpression of AIB1 and amplification of AIB1 was found in 32.5 and 7.0% of UCs, respectively. In univariate survival analysis of the UC cohorts, a highly significant association of overexpression of AIB1 with shortened patient survival (mean: 45.6 months vs. 59.0 months, p < 0.001, log rank test) was demonstrated. In different subsets of UC patients, overexpression of AIB1 was also a prognostic indicator in grade 1 (p = 0.007), grade 2 (p = 0.010) and grade 3 (p = 0.015) tumor patients, and in pTa (p = 0.025), pT2-4 (p = 0.004), pN0 (p < 0.001) and pT2-4/pN0 (p = 0.040) tumor patients. Importantly, AIB1 expression (p < 0.001) together with pT and pN status (p < 0.05) provided significant independent prognostic parameters in multivariate analysis. In addition, a significant correlation (p < 0.05) of overexpression of AIB1 with an increased UC labeling index of Ki-67 (a cell proliferation marker) was observed in these UCs. Thus, these findings provide evidence that an overexpression of AIB1, as detected by immunohistochemistry, is an independent molecular marker for poor prognosis (shortened survival time) of patients with UC.	bladder
Tumour growth inhibition by an imidazoquinoline is associated with c-Myc down-regulation in urothelial cell carcinoma.	OBJECTIVE: To detect and characterize the potential role of c-Myc in the inhibition of proliferation and induction of cell death of urothelial cell carcinoma by imidazoquinolines, Toll-like receptor-7 (TLR7) agonists, that are thought to exert their immunogenic effects through the MyD88/NF-kappaB pathway. MATERIALS AND METHODS: Human (T24) and murine (MBT-2) bladder cancer cell lines were cultured in normal culture medium or medium supplemented with imidazoquinoline. The effects of imidazoquinoline on gene expression, transcription and tumorigenesis were then evaluated. Effects of imidazoquinoline on in vivo bladder tumour growth and gene expression were investigated using a mouse model of orthotopic bladder cancer. RESULTS: There was a dose-dependent decrease in c-Myc expression in bladder cancer cells treated with imidazoquinoline; the transcriptional activity of c-Myc was also significantly reduced. Furthermore, the in vitro proliferation and tumorigenesis of MBT-2 cells were suppressed in a dose-dependent manner. For in vivo experiments, a third of mice with bladder cancer treated with intravesical imidazoquinoline showed evidence of residual bladder tumour, vs all the placebo-treated mice. In vivo expression of c-Myc, cyclin D2 and proliferating cell nuclear antigen in the bladder tumour tissue were also down-regulated. CONCLUSIONS: Imidazoquinolines can inhibit c-Myc expression and directly affect cell growth and tumorigenesis of bladder cancer cells, independent of an immune response. These direct effects might be synergistic with previously described immunogenic actions of imidazoquinolines. Our findings could broaden the potential application of imidazoquinoline therapy beyond dermatological malignancies, and further clinical studies are warranted.	bladder
Cystitis glandularis.	The cytologic finding of glandular cells in a urine specimen is unusual. The differential diagnosis ranges from benign conditions such as cystitis glandularis to adenocarcinoma. Glandular cells of cystitis glandularis with intestinal metaplasia have a bland cytologic appearance. If detected in a urine cytology specimen colonic metaplasia can be reported.	bladder
Evaluation of hypoxia-mediated growth factors in a novel bladder cancer animal model.	BACKGROUND AND AIM: The outcome of advanced transitional cell carcinoma (TCC) is poor. Changes taking place in the tumor microenvironment are receiving increased scrutiny. Hypoxia is the key to increased expression of HIF-1alpha (hypoxia-inducible factor 1alpha) resulting in increased expression of growth factors (e.g. vascular endothelial growth factor (VEGF), epidermal growth factor (EGF)). The aim of our study was to establish an animal model with modulatable tumor hypoxia. Resulting tumor growth and growth factors were assessed. MATERIALS AND METHODS: Low Hb levels were induced in rats by total body irradiation (5 Gy). Twenty animals received EPO erythropoietin (EPO), 1000 IE/kg/week subcutaneously). After subcutaneous injection of NBT-II cells a weekly determination of Hb concentration, leukocyte counts and tumor volume were performed. Serum VEGF levels were quantified and oxygen Hb saturation in healthy tissue and tumors were measured by percutaneous laser spectroscopy. HIF-1alpha and VEGF were examined immunohistochemically. RESULTS: Reduced O2 supply promoted expression of HIF-1alpha and VEGF. Low oxygen availability was essential for tumor growth. EPO improved the O2 supply and decreased expression of growth factors but did not reduce tumor volumes. CONCLUSION: Based on these studies, treatment of low Hb levels appears reasonable in TCC. O2 supply is improved and expression of tumor growth factors is decreased. Tumor volumes did not differ between the groups, causatively adverse effects of EPO overtreatment might negatively affect microcirculation. Restoring low Hb levels and improvement in the O2 supply resulted in tumor shrinkage.	bladder
Total and free PSA kinetics in patients without prostate cancer undergoing radical cystoprostatectomy.	BACKGROUND: Radical cystoprostatectomy and radical prostatectomy are the two major operations where prostate is totally and radically removed. Radical cystoprostatectomy is usually performed in patients with invasive bladder cancer. The aim of the study was to examine Total PSA, Free PSA, and Free/Total Ratio elimination kinetics after radical cystoprostatectomy. METHODS: Serum PSA, Free PSA, and Free/Total Ratio were determined preoperatively, at the time of cystoprostatectomy specimen removal and then at 3, 6, 12, 24, 48, 72, and 168 hr, from seven patients with muscle invasive bladder cancer, who underwent radical cystoprostatectomy. Free and Total PSA concentrations were measured with non-competitive immunological procedures. The elimination rates and half-lives of Total, Free PSA and Free/Total Ratio were studied using a nonlinear regression analysis. RESULTS: Surgical manipulations caused about 1.5-fold increase of PSA, 5-fold increase in Free PSA and 3-fold increase in Free/Total Ratio. PSA and Free PSA followed a biphasic elimination pattern of a rapid exponential (a) phase with a half-life of 4.27 and 2.14 hr and a terminal, nonexponential (b) phase with a half-life of 63 and 173.2 hr, respectively. Free/Total PSA Ratio followed, also, a biphasic kinetic pattern of a rapid exponential decline with a half-life of 3.34 and a terminal non-exponential increase with a doubling time of 43 hr. CONCLUSIONS: Comparing PSA kinetics after radical cystoprostatectomy with those of radical prostatectomy, it appears that PSA follows the same elimination pattern in both models. In contrast, Free PSA and Free/Total Ratio elimination kinetics' patterns differ between the two surgical models.	bladder
Genetic polymorphisms of cytochrome P450 CYP1A1 (*2A) and microsomal epoxide hydrolase gene, interactions with tobacco-users, and susceptibility to bladder cancer: a study from North India.	The role of low penetrance genes and environmental factors in the etiology of bladder cancer (CaB) is unclear, but may involve genetic and environmental factors. Most environmental pro-carcinogens require metabolic activation by phase I enzymes (CYP450s), However, phase II enzyme (i.e., microsomal epoxide hydrolase: mEH) is mainly involved in the detoxification of wide variety of endogenous or exogenous carcinogens. Genetic differences in CYP1A1 gene and the mEH gene polymorphisms have been reported to be associated with susceptibility to various cancers. In our case-control study, we assess whether Msp1 polymorphism of CYP1A1 (CYP1A1*2A), and His(113) in exon 3 and Arg(139) in exon 4 of the mEH susceptibility genotypes, tobacco-use and age factors contribute to bladder cancer risk among Indians. A case-control study was conducted in 106 bladder cancer (CaB) patients and 160 age matched controls from similar ethnic background. The CYP1A1*2A and mEH genotypes were determined by polymerase chain reaction/restriction fragment length polymorphism method from DNA extracted from peripheral blood samples. Binary logistic regression model was used for assessing differences in genotype prevalence between patients and the controls. The Arlequin software package was used to compute haplotype frequencies. We observed non-significant association in T/C polymorphism of the CYP1A1 gene (CYP1A1*2A); however, the exon 3 His genotype of the mEH gene polymorphism alone (odds ratio = 2.67, P = 0.001) or in combination with tobacco-users were significantly associated with the risk of bladder cancer. No associations were observed with stage or grade of bladder tumor with these genotypes. In conclusion, our study demonstrated that exon 3 His genotype of the mEH are more prone to the risk of sporadic bladder cancer in North India.	bladder
Hyaluronic acid synthase-1 expression regulates bladder cancer growth, invasion, and angiogenesis through CD44.	Hyaluronic acid (HA) promotes tumor metastasis and is an accurate diagnostic marker for bladder cancer. HA is synthesized by HA synthases HAS1, HAS2, or HAS3. We have previously shown that HAS1 expression in tumor tissues is a predictor of bladder cancer recurrence and treatment failure. In this study, we stably transfected HT1376 bladder cancer cells with HAS1-sense (HAS1-S), HAS1-antisense (HAS1-AS), or vector cDNA constructs. Whereas HAS1-S transfectants produced approximately 1.7-fold more HA than vector transfectants, HA production was reduced by approximately 70% in HAS1-AS transfectants. HAS1-AS transfectants grew 5-fold slower and were approximately 60% less invasive than vector and HAS1-S transfectants. HAS1-AS transfectants were blocked in G(2)-M phase of the cell cycle due to down-regulation of cyclin B1, cdc25c, and cyclin-dependent kinase 1 levels. These transfectants were also 5- to 10-fold more apoptotic due to the activation of the Fas-Fas ligand-mediated extrinsic pathway. HAS1-AS transfectants showed a approximately 4-fold decrease in ErbB2 phosphorylation and down-regulation of CD44 variant isoforms (CD44-v3, CD44-v6, and CD44-E) both at the protein and mRNA levels. However, no decrease in RHAMM levels was observed. The decrease in CD44-v mRNA levels was not due to increased mRNA degradation. Whereas CD44 small interfering RNA (siRNA) transfection decreased cell growth and induced apoptosis in HT1376 cells, HA addition modestly increased CD44 expression and cell growth in HAS1-AS transfectants, which could be blocked by CD44 siRNA. In xenograft studies, HAS1-AS tumors grew 3- to 5-fold slower and had approximately 4-fold lower microvessel density. These results show that HAS1 regulates bladder cancer growth and progression by modulating HA synthesis and HA receptor levels.	bladder
Upper urinary tract urothelial carcinoma in eastern Taiwan: high proportion among all urothelial carcinomas and correlation with chronic kidney disease.	BACKGROUND/PURPOSE: This study investigated the incidence of upper urinary tract urothelial carcinoma (UUT-UC) in eastern Taiwan and its association with chronic kidney disease (CKD). METHODS: A total of 110 patients with histologically proven UUT-UC over a recent 20-year period were retrospectively analyzed to determine the clinical profile, overall survival and correlation with CKD. RESULTS: The mean age at diagnosis was 68.7 +/- 9.8 years (range, 43-93 years), and the male to female ratio was 1 to 1.16 (51:59). The ratio of urothelial carcinoma (UC) of the renal pelvis to UC of the ureter to UC of the bladder was 1.2:1:6.7. UC of the renal pelvis accounted for 10.8% of all urinary tract UC, and for 41% of all renal cancer detected during the study period. The 2-, 5- and 10-year cancer-specific survival rates of patients with UUT-UC were 75%, 53.0% and 29%, respectively. Patients with high grade and high stage UUT-UC had significantly worse prognosis than those with low grade (p = 0.0047) and low stage (p = 0.0021). Of the 110 patients, 64 (58%) had impaired renal function (glomerular filtration rate < 60 mL/min/1.73 m2; defined as CKD), including 14 (13%) with end-stage renal disease (ESRD) before diagnosis. Patients with CKD or ESRD had significantly worse prognosis than those with normal renal function (p = 0.0399). High grade UC was found in 35 of 58 patients with CKD or ESRD (60%), which was significantly higher than in patients with normal renal function (12/26, 26%; p = 0.019). CONCLUSION: A high proportion of UUT-UC was observed among all UCs and a significantly higher percentage of high grade UUT-UC (60%) were found in patients with CKD or ESRD in eastern Taiwan. These findings suggest that CKD and ESRD might play a role in the development of UC especially in the upper urinary tract.	bladder
Hypermethylation of tumor-suppressor gene CpG islands in small-cell carcinoma of the urinary bladder.	Small-cell carcinoma of the urinary bladder (SCBC) is a rare tumor, which shows a common clonal origin with urothelial carcinoma. It bears a high metastatic potential, even when discovered in a localized state. Identifying the molecular underpinnings of this disease may elucidate useful clinical information regarding prevention, diagnosis, prognosis, treatment, and surveillance. As DNA methylation is widely recognized as having a pivotal role in the process of carcinogenesis, we analyzed the DNA methylation status of four frequently hypermethylated tumor suppressors in small-cell and transitional-cell carcinoma (TCC) arising concomitantly in 13 patients. Fourteen cases of pure TCC were also included in the analysis. We identified frequent methylation of RASSF1 and MGMT and infrequent methylation of MLH1 and DAPK1 in cases of concomitant TCC and SCBC. Similar rates of methylation were found in pure and concomitant histopathologies, with the exception of MGMT, which was much less frequently methylated in pure TCC. These findings suggest that SCBC and TCC have common origins, establish DNA methylation of some tumor suppressors as frequent occurrences in both histopathologies, and suggest that MGMT methylation may be an SCBC-specific epimutation.	bladder
Gene polymorphisms in bladder cancer.	In Europe, cancer of the bladder is the fourth most common cancer among men, accounting for 7% of total cancers. In the USA, bladder cancer is the fifth most common cancer in men and seventh in women. This disease is three times more common in men than in women. Several risk factors, such as cigarette smoking and occupational chemical exposure, contribute to bladder cancer development. The balance between activation and detoxification of carcinogens affects the amount of DNA damage that accumulates in cells. The entire process leading to DNA damage and subsequent repair of the damage involves a host of enzymes, many of which are polymorphic. Polymorphisms in metabolic enzyme genes and repair genes may cause alterations in protein product functions that can finally lead to genomic instability and carcinogenesis. In this article, we review the polymorphisms in a number of genes that have been found to be the modulators of bladder cancer risk. Improved understanding of the molecular biology of urothelial malignancies is helping to more clearly define the role of new prognostic indices and multidisciplinary treatment for this disease.	bladder
Modulation of several waves of gene expression during FGF-1 induced epithelial-mesenchymal transition of carcinoma cells.	During epithelial-mesenchymal transition (EMT), epithelial cells are converted into isolated motile and invasive mesenchymal cells. In model systems, EMT is induced most often by the activation of tyrosine kinase receptors through signaling pathways involving translational and post-translational regulation. In this study, we have used the NBT-II bladder carcinoma cell system to investigate in vitro Fibroblast Growth Factor-1 (FGF-1)-induced EMT. Transcriptome analyses were performed on NBT-II cells stimulated for 2, 6, 24, and 48 h with FGF-1. As some phenotypic changes occurred around 6 h post-stimulation, a supervised analysis was designed to identify transcript variations across defined time-periods. Our results clearly indicate that immediately after FGF-1 stimulation a set of genes assigned to transcriptional regulation (e.g., jun-B and v-ets) and to EMT induction (e.g., Notch 1) is transiently up-regulated. A set of genes involved in proteolytic systems (e.g., MMP-13 and uPAR) is immediately up-regulated but subsequently maintained throughout FGF-1 stimulation. Then follows a second wave of gene expression that includes a strong but transient up-regulation of ephrin B1 and arginase I. Finally, a third group of genes is stably modulated over 48 h which consists primarily of down-regulated genes specifically associated with the EMT-based loss of the epithelial phenotype and maintenance of the mesenchymal and invasive phenotype of carcinoma cells. Using genome-wide oligoarray technology, we have identified novel expressions of immediate, immediate-early and later EMT biomarkers that are specifically activated downstream of the FGF/FGFR pathway and which might be significant prognostic factors for tumor progression of carcinoma.	bladder